Single-cell analysis reveals the continuum of human lympho-myeloid progenitor cells

Karamitros, Dimitris; Stoilova, Bilyana; Aboukhalil, Zahra; Hamey, Fiona; Reinisch, Andreas; Samitsch, Marina; Quek, Lynn; Otto, G.; Repapi, Emmanouela; Doondeea, Jessica; Usukhbayar, Batchimeg; Calvo, Julien; Taylor, Stephen; Goardon, Nicolas; Six, Emmanuelle; Pflumio, Françoise; Porcher, Catherine; Majeti, Ravindra; Göttgens, Berthold; Vyas, Paresh

doi:10.1038/s41590-017-0001-2

Cited by 210 publications

(257 citation statements)

References 53 publications

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“…In experimental terms, this means that a phenotypically defined population does not contain a homogeneous population of multi-potent cells, but rather, a cross-section of cells primed by related but distinct developmental pathways that share a common, transient phenotype. [33][34][35][36] Entities such as the macrophage-dendritic cell progenitor (MDP) and common dendritic cell progenitor (CDP) are evanescent. Although bi-potential and tri-potential cells exist, profiling of > 2000 clonal outputs from the entire range of human progenitors does not find any significant populations corresponding to human MDP or CDP.…”

Section: Analysis Of Human Dendritic Cells Monocytes and Macrophagesmentioning

confidence: 99%

“…33,34,37 In contemporary models, lymphoid-primed multipotent progenitors are at the apex of all myeloid and lymphoid lineages. 34,36 The important consequence of this is that it is no longer necessary to puzzle over the apparent 'dual' lymphoid and myeloid origin of DC, because DC are a product of the core lympho-myeloid pathway in which both traits may be expressed by emerging progeny.…”

Section: Analysis Of Human Dendritic Cells Monocytes and Macrophagesmentioning

confidence: 99%

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Human dendritic cell subsets: an update

2018

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SummaryDendritic cells (DC) are a class of bone‐marrow‐derived cells arising from lympho‐myeloid haematopoiesis that form an essential interface between the innate sensing of pathogens and the activation of adaptive immunity. This task requires a wide range of mechanisms and responses, which are divided between three major DC subsets: plasmacytoid DC (pDC), myeloid/conventional DC1 (cDC1) and myeloid/conventional DC2 (cDC2). Each DC subset develops under the control of a specific repertoire of transcription factors involving differential levels of IRF8 and IRF4 in collaboration with PU.1, ID2, E2‐2, ZEB2, KLF4, IKZF1 and BATF3. DC haematopoiesis is conserved between mammalian species and is distinct from monocyte development. Although monocytes can differentiate into DC, especially during inflammation, most quiescent tissues contain significant resident populations of DC lineage cells. An extended range of surface markers facilitates the identification of specific DC subsets although it remains difficult to dissociate cDC2 from monocyte‐derived DC in some settings. Recent studies based on an increasing level of resolution of phenotype and gene expression have identified pre‐DC in human blood and heterogeneity among cDC2. These advances facilitate the integration of mouse and human immunology, support efforts to unravel human DC function in vivo and continue to present new translational opportunities to medicine.

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Section: Analysis Of Human Dendritic Cells Monocytes and Macrophagesmentioning

confidence: 99%

Section: Analysis Of Human Dendritic Cells Monocytes and Macrophagesmentioning

confidence: 99%

Human dendritic cell subsets: an update

2018

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“…The observed heterogeneity between patients is directly derived from differences in the LSC compartment in terms of lineage maturation, potency and the underlying molecular aberrations. A recent study suggested that normal differentiation is represented by a continuum observed on the single cell level (Karamitros et al , ), rather than discrete steps, making the matter even more complex. In addition, a variable degree of intra‐patient heterogeneity may arise from co‐existing subclones, which are frequently observed in AML (Cancer Genome Atlas Research Network, ).…”

Section: The Present Toolbox For Aml Lsc Characterisationmentioning

confidence: 99%

The concept of leukaemic stem cells in acute myeloid leukaemia 25 years on: hitting a moving target

et al. 2019

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Summary The concept of leukaemic stem cells (LSCs) was experimentally suggested 25 years ago through seminal data from John Dick's group, who showed that a small fraction of cells from acute myeloid leukaemia (AML) patients were able to be adoptively transferred into immunodeficient mice. The initial estimation of the frequency was 1:250 000 leukaemic cells, clearly indicating the difficulties ahead in translating knowledge on LSCs to the clinical setting. However, the field has steadily grown in interest, expanse and importance, concomitantly with the realisation of the molecular background for AML culminating in the sequencing of hundreds of AML genomes. The literature is now ripe with contributions describing how different molecular aberrations are more or less specific for LSCs, as well as reports showing selectivity in targeting LSCs in comparison to normal haematopoietic stem and progenitor cells. However, we argue here that these important data have not yet been fully realised within the clinical setting. In this clinically focused review, we outline the difficulties in identifying and defining LSCs at the individual patient level, with special emphasis on intraclonal heterogeneity. In addition, we suggest areas of future focus in order to realise the concept as real‐time benefit for AML patients.

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“…When cells culture in ultra-low plates, cells do not adhere to the bottom of wells. Methylcellulose-based semi solid media have also been used in a colony formation assay in some recent studies (de Sio et al, 2017;Karamitros et al, 2018).…”

Section: Colony Formation Assaymentioning

confidence: 99%

In vitro assays and techniques utilized in anticancer drug discovery

Ediriweera

Tennekoon

Samarakoon

2018

J of Applied Toxicology

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Development of a cancer is a multistep process and six major hallmarks of cancer that are known to control malignant transformation have been described. Anticancer drug development is a tedious process, requiring a number of in vitro, in vivo and clinical studies. In vitro assays provide an initial platform for cancer drug discovery approaches. A wide range of in vitro assays/techniques have been developed to evaluate each hallmark feature of cancer and selection of a particular in vitro assay or technique mainly depends on the specific research question (s) to be examined. In the present review, we have described some commonly utilized in vitro assays and techniques used to examine cell viability/proliferation, apoptosis, cellular senescence, invasion and migration, oxidative stress and antioxidant effects, gene and protein expression, angiogenesis and genomic alterations in cancer drug discovery. Additionally, uses of modern techniques such as high throughput screening, high content screening and reporter gene assays in cancer drug discovery have also been described.

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Single-cell analysis reveals the continuum of human lympho-myeloid progenitor cells

Cited by 210 publications

References 53 publications

Human dendritic cell subsets: an update

Human dendritic cell subsets: an update

The concept of leukaemic stem cells in acute myeloid leukaemia 25 years on: hitting a moving target

In vitro assays and techniques utilized in anticancer drug discovery

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